SAN FRANCISCO, CA USA (UroToday.com) - Within the last decade, despite a considerable rise in the age-adjusted incidence of prostate cancer in the United States, the incidence of prostate cancer has remained stable (180 cases per 100 000 men).
However, the incidence has significantly increased among men younger than age 50, and a majority of tumors are now classified as well- or moderately differentiated (Gleason grade ≤ 6). Moreover, the age-adjusted mortality rate in the United States has dramatically decreased by > 40%. He mentioned, that in the last decade, many clinical trials on the early detection and prevention of prostate cancer and development of novel prediction tools were published to assist clinicians with the individualization of disease management.
In regards to chemoprevention, he reviewed the unexpected results that came out of the Prostate Cancer Prevention Trial (PCPT) that was designed to evaluate the effectiveness of finasteride in reducing the detection of prostate cancer in men with low risk of disease: prostate cancer was detected by biopsy in 24.4% of the study participants, and finasteride decreased the overall relative risk of prostate cancer by 25%. The Reduction by Dutasteride of Prostate Cancer Events (REDUCE trial) examined the effects of dutasteride in a higher risk cohort, with a similar relative risk reduction of 25% and an absolute reduction of 5.1%. In both trials, however, all risk reduction occurred in men with Gleason score 5 or 6 tumors. Despite these results, the FDA did not approve the use of these medications for the prevention of prostate cancer based largely on the premise that low-grade prostate cancers pose little threat to health and should not be treated; therefore, prevention is of no value. Moreover, Dr. Scardino discussed the results from the SELECT trial (Selenium and Vitamin E Cancer Prevention): 35 533 men at low risk for prostate cancer, randomized in a double-blind design to regimens of either vitamin or to combinations of these supplements. Since no significant differences were found in rates of prostate cancer across the intervention groups, neither of the agents is recommended.
Next he discussed the topic of “early detection” of prostate cancer. In 2012 the U.S. Preventive Services Task Force recommended against PSA screening on the grounds that there is no net benefit and that the potential harms outweigh the benefits. The U.S.-based Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial found no reduction in prostate cancer-specific mortality associated with screening after a median follow-up of 10 years, but the study was flawed by pretesting with PSA in 40% of the study participants and contamination in 70% of the individuals in the “unscreened” control cohort. Albeit, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a statistically significant 21% reduction in prostate cancer mortality at 11 years. Moreover, in a modeling study of the ERSPC trial, over the lifetime, 5 cancers needed to be detected of the screened subjects to prevent one death from prostate cancer. He then discussed the fact that case-controlled studies have shown that PSA levels at mid-life (ages 45 to 60) strongly predicted prostate cancer metastases and death over the next 25 years, suggesting that PSA testing should not be abandoned but should be used more appropriately to risk-adjust screening strategies.
With respect to active surveillance (AS) in prostate cancer, large cohorts of men with low-risk prostate cancer are being enrolled in AS programs. Studies have shown that 40% to 50% of cancers in the United States have low-risk characteristics and pose little immediate threat to life, and those cancers that do appear to progress generally respond to delayed treatment with surgery or radiation. He mentioned that efforts are needed to standardize the evaluation and follow-up of men on AS, and to define the criteria for eligibility as well as pertinent triggers for intervention. Over the last few years, a majority of radical prostatectomies in U.S. are being done with the use of robotic-assisted laparoscopic approach. In the absence of any randomized trials, evidence on outcomes of either open or robotic approach is documented in population-based observational studies and single-institution case series only. The bottom line is that the skill level of the surgeon, independent of surgical approach, has a major effect on prostate cancer treatment outcomes. Advanced imaging modalities could provide standard, reliable methods for accurately identifying tumor size, location, and extent. Over the past decade, multiparametric MRI has emerged as the most accurate imaging technique for detecting clinically important prostate cancers.
In regards to molecular and genetic studies in prostate cancer, Dr. Scardino acknowledged that a landmark discovery in the past decade was the identification of a chromosomal rearrangement in an androgen-regulated gene. Transmembrane protease serine 2 (TMPRSS2) fusion with ERG, an erythroblast transformation-specific (ETS) transcription factor family member, is identified in approximately 50% of primary and metastatic prostate cancer tumors and is most often correlated with poor prognosis. Also within the last decade, targeted sequencing of exons located on chromosome 17q21-22, resulted in the identification of a recurrent mutation in HOXB13, the first gene associated with risk of hereditary prostate cancer. He concluded by saying that in the near future, use of molecular and genetic tests, improvements in the quality of care through reliable metrics of performance and feedback to physicians, and the continuing evolution of surgical technology and advanced imaging will provide the road to better detection and management in prostate cancer.
Highlights of a presentation by Behfar Ehdaie, MD, MPH* and Peter T. Scardino, MD, FACS** at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
* Sidney Kimmel Center for Prostate and Urologic Cancers, New York, NY USA
**Memorial Sloan-Kettering Cancer Center, New York, NY USA